Chapter XXXIV: Part VI: Alkaloids and Poisonous Vegetable Principles Separated for the (8)

The atropine may be farther purified by converting it into oxalate, dissolving the oxalate in as small a quantity of alcohol as possible, and precipitating the oxalate out with ether; the precipitate is collected, dissolved in as small a quantity of water as possible, the water made alkaline, and the base shaken out with ether.

The most reliable test for atropine, or one of the mydriatic alkaloids, is its action on the iris; a solution of atropine, even so weak as 1 : 130,000, causing dilatation.[489] This action on the iris has been studied by Ruyter,[490] Donders, and von Graefe.

[489] _De Actione Atropæ Belladonnæ in Iridem_, Traj. ad Rhen., 1852.

[490] _Arch. Ophthal._, ix. 262, 1864.

The action is local, taking effect when in dilute solution only on the eye to which it has been applied; and it has been produced on the eyes of frogs, not only in the living subject, but after the head has been severed from the body and deprived of brain. The thinner the cornea, the quicker the dilatation; therefore, the younger the person or animal, the more suitable for experiment. In frogs, with a solution of 1 : 250, dilatation commences in about five minutes; in pigeons, seven minutes; and in rabbits, ten minutes. In man, a solution of 1 : 120 commences to act in about six to seven minutes, reaches its highest point in from ten to fifteen minutes, and persists more or less for six to eight days. A solution of 1 : 480 acts first in fifteen to twenty minutes, and reaches its greatest point in twenty minutes; a solution of 1 : 48,000 requires from three-quarters of an hour to an hour to show its effect. Dogs and cats are far more sensible to its influence than man, and therefore more suitable for experiment. If the expert chooses, he may essay the proof upon himself, controlling the dilatation by Calabar bean; but it is seldom necessary or advisable to make personal trials of this nature.[491]

[491] A. Ladenburg (_Compt. Rend._, xc. 92), having succeeded in reproducing atropine by heating tropine and tropic acid with hydrochloric acid, by substituting various organic acids for the tropic acid, has obtained a whole series of compounds to which he has given the name of _tropeines_. One of these, hydroxytoluol (amygdalic) tropeine, he has named _homatropine_. It dilates the pupil, but is less poisonous than atropine.

§ 446. =Statistics of Atropine Poisoning.=--Since atropine is the active principle of belladonna and datura plants, and every portion of these--root, seeds, leaves, and fruit--has caused toxic symptoms, poisoning by any part of these plants, or by their pharmaceutical or other preparations, may be considered with strict propriety as atropine poisoning. Our English death statistics for the ten years ending 1892, record 79 deaths (50 males and 29 females) from atropine (for the most part registered under the head of belladonna); 29 (or 36·7 per cent.) were suicidal, the rest accidental.

The greatest number of the accidental cases arise from mistakes in pharmacy; thus, belladonna leaves have been supplied for ash leaves; the extract of belladonna has been given instead of extract of juniper; the alkaloid itself has been dispensed in mistake for theine;[492] a more curious and marvellously stupid mistake is one in which it was dispensed instead of assafœtida (Schauenstein, _op. cit._, p. 652). Further, valerianate of atropine has been accidentally substituted for quinine valerianate, and Schauenstein relates a case in which atropine sulphate was administered subcutaneously instead of morphine sulphate; but the result was not lethal. Many other instances might be cited. The extended use of atropine as an external application to the eye naturally gives rise to a few direct and indirect accidents. Serious symptoms have arisen from the solution reaching the pharynx through the lachrymal duct and nose. A curious indirect poisoning, caused by the use of atropine as a collyrium, is related by Schauenstein.[493] A person suffered from all the symptoms of atropine poisoning; but the channel by which it had obtained access to the system was a great mystery, until it was traced to some coffee, and it was then found that the cook had strained this coffee through a certain piece of linen, which had been used months before, soaked in atropine solution, as a collyrium, and had been cast aside as of no value.

[492] Hohl, _De Effectu Atropini. Diss. Halle_, 1863.

[493] Maschka’s _Handbuch_.

§ 447. =Accidental and Criminal Poisoning by Atropine.=--External applications of atropine are rapidly absorbed, _e.g._, if the foot of a rat be steeped for a little while in a solution of the alkaloid, and the eyes watched, dilatation of the pupils will soon be observed. If the skin is broken, enough may be absorbed to cause death. A case is on record in which ·21 grm. of atropine sulphate, applied as an ointment to the abraded skin, was fatal.[494] Atropine has also been absorbed from the bowel; in one case, a clyster containing the active principles of 5·2 grms. (80 grains) of belladonna root was administered to a woman twenty-seven years of age, and caused death. Allowing the root to have been carefully dried, and to contain ·21 per cent. of alkaloid, it would seem that so little as 10·9 mgrms. (·16 grain) may even prove fatal, if left in contact with the intestinal mucous membrane. Belladonna berries and stramonium leaves and seeds are eaten occasionally by children. A remarkable series of poisonings by belladonna berries occurred in London during the autumn of 1846.

[494] Ploss, _Zeitschr. f. Chir._, 1863.

Criminal poisoning by atropine in any form is of excessive rarity in Europe and America, but in India it has been frightfully prevalent. In all the Asiatic cases the substance used has been one of the various species of datura, and mostly the bruised or ground seeds, or a decoction of the seeds. In 120 cases recorded in papers and works on Indian toxicology, I find no less than 63 per cent. of the cases criminal, 19 per cent. suicidal, and 18 per cent. accidental. In noting these figures, however, it must be borne in mind that known criminal cases are more certain to be recorded than any other cases. The drug has been known under the Sanscrit name of _dhatoora_ by the Hindoos from most remote times. It was largely used by the Thugs, either for the purpose of stupefying their victim or for killing him; by loose wives to ensure for a time the fatuity of their husbands; and, lastly, it seems in Indian history to have played the peculiar _rôle_ of a state agent, and to have been used to induce the idiocy or insanity of persons of high rank, whose mental integrity was considered dangerous by the despot in power. The Hindoos, by centuries of practice, have attained such dexterity in the use of the “datura” as to raise that kind of poisoning to an art, so that Dr. Chevers, in his _Medical Jurisprudence for India_,[495] declares that “there appears to be no drug known in the present day which represents in its effects so close an approach to the system of slow poisoning, believed by many to have been practised in the Middle Ages, as does the datura.”

[495] Dr. Chevers’s work contains a very good history of datura criminal poisoning.

§ 448. =Fatal Dose.=--It is impossible to state with precision the exact quantity which may cause death, atropine being one of those substances whose effect, varying in different cases, seems to depend on special constitutional tendencies or idiosyncracies of the individual. Some persons take a comparatively large amount with impunity, while others scarcely bear a very moderate dose without exhibiting unpleasant symptoms. Eight mgrms. (⅛ grain) have been known to produce poisonous symptoms, and ·129 grm. (2 grains) death. We may, therefore, infer that about ·0648 grm. (1 grain) would, unchecked by remedies, probably act fatally; but very large doses have been recovered from, especially when treatment has been prompt.

Atropine is used in veterinary practice, from 32·4 to 64·8 mgrms. (½ to 1 grain) and more being administered subcutaneously to horses; but the extent to which this may be done with safety is not yet established.

§ 449. =Action on Animals.=--The action of atropine has been studied on certain beetles, on reptiles (such as the salamander, triton, frogs, and others), on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs, and cats. Among the mammalia there is no essential difference in the symptoms, but great variation in the relative sensibility; man seems the most sensitive of all, next to man come the carnivora, while the herbivora, and especially the rodents, offer a considerable resistance. According to Falck the lethal dose for a rabbit is at least ·79 mgrm. per kilo. It is the general opinion that rabbits may eat sufficient of the belladonna plant to render their flesh poisonous, and yet the animals themselves may show no disturbance in health; but this must not be considered adequately established. Speaking very generally, the higher the animal organisation the greater the sensibility to atropine. Frogs are affected in a peculiar manner. According to the researches of Fraser,[496] the animal is first paralysed, and some hours after the administration of the poison lies motionless, the only signs of life being the existence of a slight movement of the heart and muscular irritability. After a period of from forty-eight to seventy-two hours, the fore limbs are seized with tetanic spasms, which develop into a strychnine-like tetanus.

[496] _Transact. of Edin. Roy. Soc._, vol. xxv. p. 449. _Journ. of Anat. and Physiol._, May 1869, p. 357.

§ 450. =Action on Man.=--When atropine is injected subcutaneously, the symptoms, as is usually the case with drugs administered in this manner, may come on immediately, the pupil not unfrequently dilating almost before the injection is finished. This is in no way surprising; but there are instances in which decoctions of datura seeds have been administered by the stomach, and the commencement of symptoms has been as rapid as in poisoning by oxalic or even prussic acid. In a case tried in India in July 1852, the prosecutor declared that, while a person was handing him a _lota_ of water, the prisoner snatched it away on pretence of freeing the water from dirt or straws, and then gave it to him. He then drank only two mouthfuls, and, complaining of the bitter taste, fell down insensible within forty yards of the spot where he had drunk, and did not recover his senses until the third day after. In another case, a man was struck down so suddenly that his feet were scalded by some hot water which he was carrying.--_Chevers._

When the seeds, leaves, or fruit of atropine-holding plants are eaten, there is, however, a very appreciable period before the symptoms commence, and, as in the case of opium poisoning, no very definite rule can be laid down, but usually the effects are experienced within half an hour. The first sensation is dryness of the mouth and throat; this continues increasing, and may rise to such a degree that the swallowing of liquids is an impossibility. The difficulty in swallowing does not seem to be entirely dependent on the dry state of the throat, but is also due to a spasmodic contraction of the pharyngeal muscles. Tissore[497] found in one case such constriction that he could only introduce emetics by passing a catheter of small diameter. The mucous membrane is reddened, and the voice hoarse.[498] The inability to swallow, and the changed voice, bear some little resemblance to hydrophobia--a resemblance heightened to the popular mind by an inclination to bite, which seems to have been occasionally observed; the pupils are early dilated, and the dilatation may be marked and extreme; the vision is deranged, letters and figures often appear duplicated; the eyeballs are occasionally remarkably prominent, and generally congested; the skin is dry, even very small quantities of atropine arresting the cutaneous secretion; in this respect atropine and pilocarpine are perfect examples of antagonism. With the dryness of skin, in a large percentage of cases, occurs a scarlet rash over most of the body. This is generally the case after large doses, but Stadler saw the rash produced on a child three months old by ·3 mgrm. of atropine sulphate. It appeared three minutes after the dose, lasted five hours, and was reproduced by a renewed dose.[499] The temperature of the body with large doses is raised; with small, somewhat lowered. The pulse is increased in frequency, and is always above 100--mostly from 115 to 120, or even 150, in the minute. The breathing is at first a little slowed, and then very rapid. Vomiting is not common; the sphincters may be paralysed so that the evacuations are involuntary, and there may be also spasmodic contractions of the urinary bladder. The nervous system is profoundly affected; in one case there were clonic spasms,[500] in another,[501] such muscular rigidity, that the patient could with difficulty be placed on a chair. The lower extremities are often partly paralysed, there is a want of co-ordination, the person reels like a drunken man, or there may be general jactitation. The disturbance of the brain functions is very marked; in about 4 per cent. only of the recorded cases has there been no delirium, or very little--in the majority delirium is present. In adults this generally takes a garrulous, pleasing form, but every variety has been witnessed. Dr. H. Giraud describes the delirium from datura (which it may be necessary to again repeat is _atropine_ delirium) as follows:--“He either vociferates loudly or is garrulous, and talks incoherently; sometimes he is mirthful, and laughs wildly, or is sad and moans, as if in great distress; generally he is observed to be very timid, and, when most troublesome and unruly, can always be cowed by an angry word, frequently putting up his hands in a supplicating posture. When approached he suddenly shrinks back as if apprehensive of being struck, and frequently he moves about as if to avoid spectra. But the most invariable accompaniment of the final stage of delirium, and frequently also that of _sopor_, is in the incessant picking at real or imaginary objects. At one time the patient seizes hold of parts of his clothes or bedding, pulls at his fingers and toes, takes up dirt and stones from the ground, or as often snatches at imaginary objects in the air, on his body, or anything near him. Very frequently he appears as if amusing himself by drawing out imaginary threads from the ends of his fingers, and occasionally his antics are so varied and ridiculous, that I have seen his near relatives, although apprehensive of danger, unable to restrain their laughter.”[502] This active delirium passes into a somnolent state with muttering, catching at the bedclothes, or at floating spectra, and in fatal cases the patient dies in this stage. As a rule, the sleep is not like opium coma; there is complete insensibility in both, but in the one the sleep is deep, without muttering, in the other, from atropine, it is more like the stupor of a fever. The course in fatal cases is rapid, death generally taking place within six hours. If a person live over seven or eight hours, he usually recovers, however serious the symptoms may appear. On waking, the patient remembers nothing of his illness; mydriasis remains some time, and there may be abnormality of speech and weakness of the limbs, but within four days health is re-established. In cases where the seeds have been swallowed, the symptoms may be much prolonged, and they seem to continue until all the seeds have been voided--perhaps this is due to the imperfect but continuous extraction of atropine by the intestinal juices.

[497] _Gaz. hebd._, 1856.

[498] A friend of the author’s was given, by a mistake in dispensing, 16 minims of a solution of atropine sulphate, equivalent to 1/7 grain of atropine (or 9·3 mgrms). Ten minutes after taking the dose there was dilatation of the pupil, indistinctness of vision, with great dryness of the throat and difficulty in swallowing; he attempted to eat a biscuit, but, after chewing it, he was obliged to spit it out, as it was not possible to swallow; the throat was excessively sore, and there was a desire to pass urine, but only a few drops could be voided. In forty-five minutes he was unable to stand or walk. There was a bright rash on the chest. In two hours he became insensible, and was taken to the Middlesex Hospital, recovering under treatment in about eight hours.

[499] _Med. Times_, 1868.

[500] _Lancet_, vol. i., 1881, p. 414.

[501] _Ibid._, vol. i., 1876, p. 346.

[502] In an English case of belladonna poisoning, the patient, a tailor, sat for four hours, moving his hands and arms as if sewing, and his lips as if talking, but without uttering a word.

Chronic poisoning by atropine may, from what has been stated, be of great importance in India. It is probable that its continuous effect would tend to weaken the intellect, and there is no reason for any incredulity with regard to its power as a factor of insanity. Rossbach has ascertained that if dogs are, day after day, dosed with atropine, they become emaciated; but a certain tolerance is established, and the dose has to be raised considerably after a time to produce any marked physiological effect.

§ 451. =Physiological Action of Atropine.=--From the numerous experiments on animals which have been performed for the purpose of elucidating the action of atropine, it is clear that the terminations of the vagus in the heart muscle are first excited, and then paralysed. The excitor-motor ganglion is also paralysed, and finally the heart itself; death resulting from heart paralysis. The respiratory disturbance is also to be ascribed to the vagus; the terminations in the lung are paralysed, and, at the same time, the poison circulating through the respiratory nervous centre stimulates it first, and then it also becomes finally paralysed. The small vessels are generally widened after a previous transitory narrowing. Organs containing unstriped muscular fibre are generally paralysed, as well as the ends of the nerves regulating secretion--hence the dryness of the skin. The action on the iris is not thoroughly elucidated.

§ 452. The _diagnosis_ of atropine poisoning may be very difficult unless the attention of the medical man be excited by some suspicious circumstance. A child suffering from belladonna rash, with hot dry skin, quick pulse, and reddened fauces, looks not unlike one under an attack of scarlet fever. Further, as before mentioned, some cases are similar to rabies; and again, the garrulous delirium and the hallucinations of an adult are often very similar to those of _delirium tremens_, as well as tomania.

§ 453. =Post-mortem Appearances.=--The _post-mortem_ appearances do not seem to be characteristic, save in the fact that the pupils remain dilated. The brain is usually hyperæmic, and in one case the absence of moisture seems to have been remarkable. The stomach and intestines may be somewhat irritated if the seeds, leaves, or other parts of the plant have been eaten; but the irritation is not constant if the poisoning has been by pure atropine, and still less is it likely to be present if atropine has been administered subcutaneously.

§ 454. =Treatment.=--The great majority of cases recover under treatment. In 112 cases collected by F. A. Falck, 13 only were fatal (11·6 per cent.). The greater portion of the deaths in India are those of children and old people--persons of feeble vitality. The Asiatic treatment, which has been handed down by tradition, is the application of cold water to the feet; but the method which has found most favour in England is treatment by pilocarpine, a fifth of a grain or more being injected from time to time. Pilocarpine shows as perfect antagonism as possible; atropine dries, pilocarpine moistens the skin; atropine accelerates, pilocarpine slows the respiration. Dr. Sydney Ringer and others have published a remarkable series of cases showing the efficacy of this treatment, which, of course, is to be combined where necessary with emetics, the use of the stomach-pump, &c.[503]

[503] See, for Dr. Ringer’s cases, _Lancet_, vol. i., 1876, p. 346. Refer also to _Brit. Med. Journ._, vol. i., 1881, p. 594; _ib._, p. 659.

§ 455. =Separation of Atropine from Organic Tissues, &c.=--From the contents of the stomach, atropine may be separated by acidulating strongly with sulphuric acid (15 to 20 c.c. of dilute H₂SO₄ to 100 c.c.), digesting for some time at a temperature not exceeding 70°, and then reducing any solid matter to a pulp by friction, and filtering, which can generally be effected by the aid of a filter-pump. The liver, muscles,[504] and coagulated blood, &c., may also be treated in a precisely similar way. The acid liquid thus obtained, is first, to remove impurities, shaken up with amyl alcohol, and after the separation of the latter in the usual manner, it is agitated with chloroform, which will take up any of the remaining amyl alcohol,[505] and also serve to purify further. The chloroform is then removed by a pipette (or the separating flask before described), and the fluid made alkaline, and shaken up with ether, which, on removal, is allowed to evaporate spontaneously. The residue will contain atropine, and this may be farther purified by converting it into oxalate, as suggested, page 374.

[504] Neither amyl alcohol nor chloroform removes atropine from an _acid_ solution.

[505] Atropine goes into the blood, and appears to be present in the different organs in direct proportion to the quantity of blood they contain. Dragendorff has found in the muscles of rabbits fed upon belladonna sufficient atropine for quantitative estimation.

From the urine,[506] atropine may be extracted by acidifying with sulphuric acid, and agitation with the same series of solvents. Atropine has been separated from putrid matters long after death, nor does it appear to suffer any decomposition by the ordinary analytical operations of evaporating solutions to dryness at 100°. In other words, there seems to be no necessity for operations _in vacuo_, in attempts at separating atropine.

[506] Dragendorff has found atropine in the urine of rabbits fed with belladonna; the separation by the poison is so rapid that it often can only be recognised in the urine during the first hour after the poison has been taken.

TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE HENBANE PLANT.

+----------------------------+-------+-------+-------+-------+
| | Seeds,|Leaves,| Stalk,| Root, |
+----------+---------+-------+-------+-------+-------+-------+
| Plant | Hyosc.- | 1868. | ... | 0·588 | 0·012 | 0·128 |
| Desti- | Albus. | 1869. | ... | 0·469 | ... | 0·176 |
| tute +---------+-------+-------+-------+-------+-------+
| of | Hyosc.- | 1868. | ... | 0·154 | 0·070 | 0·027 |
| Flowers. | Niger. | 1869. | ... | 0·192 | 0·017 | 0·080 |
+----------+---------+-------+-------+-------+-------+-------+
| | Hyosc.- | 1868. | ... | 0·359 | 0·036 | 0·146 |
| Plant | Albus. | 1869. | ... | 0·329 | 0·048 | 0·262 |
| in +---------+-------+-------+-------+-------+-------+
| Flower. | Hyosc.- | 1868. | ... | 0·147 | 0·032 | 0·127 |
| | Niger. | 1869. | ... | 0·206 | 0·030 | 0·138 |
+----------+---------+-------+-------+-------+-------+-------+
| | Hyosc.- | 1868. | 0·162 | 0·211 | 0·027 | 0·106 |
| Plant | Albus. | 1869. | 0·172 | 0·153 | 0·029 | 0·086 |
| in +---------+-------+-------+-------+-------+-------+
| Fruit. | Hyosc.- | 1868. | 0·075 | 0·065 | 0·009 | 0·028 |
| | Niger. | 1869. | 0·118 | 0·110 | 0·010 | 0·056 |
+----------+---------+-------+-------+-------+-------+-------+

2. HYOSCYAMINE.

§ 456. This powerful alkaloid is contained in small quantities in datura and belladonna, and also is found in the common lettuce (·001 per cent.),[507] and in _Scopola carmolica_, a solanaceous plant indigenous to Austria and Hungary[508]; but its chief source is the _Hyoscyamus niger_ and _Hyoscyamus alba_ (black and white henbane): it is also found in the _Duboisia myoporoides_. The latter plant was considered to contain a new alkaloid, “_Duboisine_,” but duboisine is a mixture of hyoscyamine and hyoscine. Ladenburg’s hyoscine accompanies hyoscyamine, and is an isomeride of both atropine and hyoscyamine; its chemical reactions are similar to those of hyoscyamine, as well as its physiological effects.[509]

[507] T. S. Dymond, _Journ. Chem. Soc. Trans._, 1892, 90.

[508] W. R. Dunstan and A. E. Chaston. _Pharm. Journ. Trans._ (3), xx. 461-464.

[509] See _Ber. der deutsch. Chem. Gesell._, 13, 1549 to 1554. By boiling hyoscine hydrochloride with animal charcoal, and then precipitating with auric chloride, a good crystalline compound, melting at 198°, can be obtained.

=Hyoscyamine= (C₁₇H₂₃NO₃), as separated in the course of analysis, is a resinoid, sticky, amorphous mass, difficult to dry, and possessing a tobacco-like odour. It can, however, be obtained in well-marked odourless crystals, which melt at 108°-109°, a portion subliming unchanged. It liquefies under boiling water without crystallisation. According to Thorey,[510] hyoscyamine crystallises out of chloroform in rhombic tables, and out of benzene in fine needles; but out of ether or amyl alcohol it remains amorphous. When perfectly pure, it dissolves with difficulty in cold, but more readily in hot, water; if impure, it is hygroscopic, and its solubility is much increased. In any case, it dissolves easily in alcohol, ether, chloroform, amyl alcohol, benzene, and dilute acids. Hyoscyamine neutralises acids fully, and forms crystallisable salts, which assume for the most part the form of needles. It is isomeric with atropine, and is converted into atropine by heating to 110°, or warming with alcoholic potash. The gold salt melts at 159°, and does not melt in boiling water like the atropine gold salt.

[510] _Pharm. Zeitschr. f. Russl._, 1869.

§ 457. =Pharmaceutical and other Preparations of Henbane.=--The leaves are alone officinal in the European pharmacopœias; but the seeds and the root, or the flowers, may be met with occasionally, especially among herbalists. The table[511] (p. 382) will give an idea of the alkaloidal content of the different parts of the plant.

[511] This table, taken from Dragendorff’s _Chemische Werthbestimmung einiger starkwirkenden Droguen_, embodies the researches of Thorey.

In order to ascertain the percentage of the alkaloid in any part of the plant, the process followed by Thorey has the merit of simplicity. The substance is first exhausted by petroleum ether, which frees it from fat; after drying, it is extracted with 85 per cent. alcohol at a temperature not exceeding 40°. The alcoholic extracts are then united, the alcohol distilled off, and the residue filtered. The filtrate is now first purified by agitation with petroleum ether, then saturated by ammonia, and shaken up with chloroform. The latter, on evaporation, leaves the alkaloid only slightly impure, and, after washing with distilled water, if dissolved in dilute sulphuric acid, a crystalline sulphate may be readily obtained.

=A tincture and an extract of henbane leaves and flowering tops= are officinal in most pharmacopœias; an extract of the seeds in that of France.

=An oil of hyoscyamus= is officinal in all the Continental pharmacopœias, but not in the British.

=Henbane juice= is recognised by the British pharmacopœia; it is about the same strength as the tincture.

=An ointment=, made of one part of the extract to nine of simple ointment, is officinal in the German pharmacopœia.

The tincture (after distilling off the spirit) and the extracts (on proper solution) may be conveniently titrated by Mayer’s reagent (p. 263), which, for this purpose, should be diluted one-half; each c.c. then, according to Dragendorff, equalling 6·98 mgrms. of hyoscyamine. Kruse found 0·042 per cent. of hyoscyamine in a Russian tincture, and ·28 per cent. in a Russian extract. Any preparation made with extract of henbane will be found to contain nitrate of potash, for Attfield has shown the extract to be rich in this substance. The ointment will require extraction of the fat by petroleum ether; this accomplished, the determination of its strength is easy.

=The oil of hyoscyamus= is poisonous, and contains the alkaloid. An exact quantitative research is difficult; but if 20 grms. of the oil are shaken up for some time with water acidified by sulphuric acid, the fluid separated from the oil, made alkaline, shaken up with chloroform, and the latter removed and evaporated, sufficient will be obtained to test successfully for the presence of the alkaloid, by its action on the pupil of the eye.

§ 458. =Dose and Effects.=--The dose of the uncrystalline hyoscyamine is 6 mgrms. (1/10 grain), carefully increased. I have seen it extensively used in asylums to calm violent or troublesome maniacs. Thirty-two mgrms. (½ grain) begin to act within a quarter of an hour; the face flushes, the pupils dilate, there is no excitement, all muscular motion is enfeebled, and the patient remains quiet for many hours, the effects from a single dose not uncommonly lasting two days. 64·8 mgrms. (1 grain) would be a very large, and possibly fatal, dose. The absence of delirium or excitement, with full doses of hyoscyamine, is a striking contrast to the action of atropine, in every other respect so closely allied; yet there are cases on record showing that the henbane root itself has an action similar to that of belladonna, unless indeed one root has been mistaken for another; _e.g._, Sonnenschein relates the following ancient case of poisoning:--In a certain cloister the monks ate by error the root of henbane. In the night they were all taken with hallucinations, so that the pious convent was like a madhouse. One monk sounded at midnight the matins, some who thereupon came into chapel could not read, others read what was not in the book, others sang drinking songs--in short, there was the greatest disturbance.

§ 459. =Separation of Hyoscyamine from Organic Matters.=--The isolation of the alkaloid from organic tissues or fluids, in cases where a medicinal preparation of henbane, or of the leaves, root, &c., has been taken, is possible, and should be carried out on the principles already detailed. Hyoscyamine is mainly identified by its power of dilating the pupil of the eye. It is said that so small a quantity as ·0083 mgrm. (1/4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is true that atropine also dilates the pupil; but if sufficient of the substance should have been isolated to apply other tests, it can be distinguished from atropine by the fact that the latter gives no immediate precipitate with platinic chloride, whilst hyoscyamine is precipitated by a small quantity of platinic chloride, and dissolved by a larger amount, and also by the characters of the gold salt.

3. HYOSCINE.

§ 460. =Hyoscine=, C₁₇H₂₃NO₃.--According to E. Schmidt[512] the
formula is C₁₇H₂₁NO₄ + H₂O, and the alkaloid is identical with
scopolamine. Scopolamine has a m.p. of 59°, gives an aurochloride,
crystallising in needles, the m.p. of which is 212° to 214°; when
boiled with baryta water, it splits up into atropic acid and
scopoline, a base (C₈H₁₃NO), m.p. 110°, boiling-point, 241° to 243°;
scopoline forms an aurochloride, m.p. 223°-225°; and a
platinochloride, m.p. 228°-230°; but Ladenburg,[513] in answer to
Schmidt, asserts that hyoscine exists, and is not identical with
scopolamine. A sample of commercial hyoscine hydrobromide Nagelvoort
found to melt, water-free, at 198°; other commercial samples of
hydrobromide melted at 179° and 186°; the latter sample giving an
aurochloride which melted at 192°. Pure hyoscine gold chloride is
stated to melt at 198°. Its reactions are much the same as those of
atropine, but it does not blacken calomel. It is very poisonous.

[512] _Arch. Pharm._, ccxxx. 207-231.

[513] _Ber._, xxv. 2388-2394.

According to experiments on animals, the heart is first slowed, then
quickened; the first effect being due to a stimulation of the
inhibitory nervous apparatus, the second to a paralysing action on
the same. The temperature is not altered. The pupils are dilated,
the saliva diminished. The irritability of the brain is
lessened.[514]

[514] Parloff, _St Petersburg Med. Chem. Acad._, Dissert. No. 9, 1889-90.

4. SOLANINE.

§ 461. =Distribution of Solanine.=--Solanine is a poisonous
nitrogenised glucoside found in all parts of the plants belonging to
the nightshade order. The English common plants in which solanine
occurs are the edible potato plant (_Solanum tuberosum_), the
nightshade (_Solanum nigrum_), and the _Solanum dulcamara_, or
bitter-sweet. The berries of the _Solanum nigrum_ and those of _S.
dulcamara_ contain about 0·3 per cent. Mature healthy potatoes
appear to contain no solanine, but from 150 grms. of diseased
potatoes G. Kassner[515] separated 30 to 50 mgrms.

[515] _Arch. Pharm._ (3), xxv. 402, 403.

R. Firbas,[516] in a research on the active substances or young
shoots of the _S. tuberosum_ found two products--one crystalline,
_Solanine_; the other amorphous, _Solaneine_. He gives the following
formula to solanine--C₅₂H₉₃NO₁₈4½H₂O; when dried at 100° it becomes
anhydrous. From a solution in 85 per cent. alcohol it crystallises
in colourless needles, m.p. 244°; these are almost insoluble in
ether and alcohol, but are readily dissolved in dilute hydrochloric
acid. On hydrolysis solanine breaks up into solanidine and a sugar,
according to the equation--

[516] _Monatsh._, x. 541-560; _Journ. Chem. Soc._ (Abst.), Jan. 1890.

C₅₂H₉₃NO₁₈ = C₄₀H₆₁NO₂ + 2C₆H₁₂O₆ + 4H₂O.

§ 462. =Properties of Solanine.=--The reaction of the crystals is
weakly alkaline; the taste is somewhat bitter and pungent. Solanine
is soluble in 8000 parts of boiling water, 4000 parts of ether, 500
parts of cold, and 125 of boiling alcohol. It dissolves well in hot
amyl alcohol, but is scarcely soluble in benzene. An aqueous
solution froths on shaking, but not to the degree possessed by
saponine solutions.

The amyl alcohol solution has the property of gelatinising when
cold. It does this if even so little as 1 part of solanine is
dissolved in 2000 of hot amyl alcohol. The jelly is so firm that the
vessel may be inverted without any loss. This peculiar property is
one of the most important tests for the presence of solanine. The
hot ethylic alcohol solution will, on cooling, also gelatinise, but
a stronger solution is required. From very dilute alcoholic
solutions (and especially with slow cooling) solanine may be
obtained in crystals. In dilute mineral acids solanine dissolves
freely, and forms salts, which for the most part have an acid
reaction and are soluble in alcohol and in water, but with
difficulty in ether. The compounds with the acids are not very
stable, and several of them are broken up on warming the solution,
solanine separating out from the aqueous solutions of the solanine
salts. The alkaloid may be precipitated by the fixed and volatile
alkalies, and by the alkaline earths. Solanine will stand boiling
with strongly alkaline solutions without decomposition; but dilute
acids, on warming, hydrolyse. By heating solanine in alcoholic
solution with ethyl iodide in closed tubes, and then treating the
liquid with ammonia, ethyl solanine in well-formed crystals can be
obtained. Solanine is precipitated by phosphomolybdic acid, but by
very few other substances. It gives, for example, no precipitate
with the following reagents:--Platinic chloride, gold chloride,
mercuric chloride, potassic bichromate, and picric acid. Tannin
precipitates it only after a time. Sodic phosphate gives a
crystalline precipitate of solanine phosphate, if added to a
solution of solanine sulphate. Both solanine and solanidine give
with nitric acid at first a colourless solution, which, on gentle
warming, passes into blue, then into light red, and lastly becomes
weakly yellow. Solanine, dissolved in strong sulphuric acid, to
which a little Fröhde’s reagent is added, at first colours the fluid
light brown; after standing some time the edges of the drop becomes
reddish-yellow, and finally the whole a beautiful cherry-red, which
gradually passes into dark violet when violet-coloured flocks
separate.

§ 463. =Solanidine.=--Solanidine has stronger basic properties than
solanine. Its formula is C₄₀H₆₁NO₂. It is obtained from an alcoholic
solution in amorphous masses interspersed with needles; m.p. 191°.
It dissolves readily in hot alcohol, with difficulty in ether. With
hydrochloric acid it forms a hydrochloride--3(C₄₀H₆₁NO₂HCl)HCl + H₂O
or 1½H₂O. This hydrochloride is a slightly yellow powder, only
sparingly soluble in water, and carbonising without melting when
heated to 287°. Solanidine also forms a sulphate,
3(C₄₀H₆₁NO₂H₂SO₄)H₂SO₄ + 8H₂O; this salt is in the form of scaly
plates, melting at 247°; it dissolves readily in water.

The sugar obtained from the hydrolysis of solanidine is a yellow
amorphous mass dissolving readily in water and wood spirit, and has
a specific rotatory power of [α]_{D} = + 28·623. With
Phenylhydrazine hydrochloride and sodium acetate in aqueous solution
it forms a glucosazone, melting at 199°. It is probably a mixture of
sugars.

Solaneine is the name that has been given to the amorphous substance
accompanying solanine; on hydrolysis it yields solanidine and the
same sugar as solanine. Its formula is C₅₂H₈₂NO₁₃ with 4H₂O.

§ 464. =Poisoning from Solanine.=--Poisoning from solanine has been,
in all recorded cases, induced, not by the pure alkaloid (which is
scarcely met with out of the laboratory of the scientific chemist),
but by the berries of the different species of _Solanum_, and has
for the most part been confined to children. The symptoms in about
twenty cases,[517] which may be found detailed in the medical
literature of this century, have varied so greatly that the most
opposite phenomena have been witnessed as effects of poisoning by
the same substance. The most constant phenomena are a quick pulse,
laboured respiration, great restlessness, and hyperæsthesia of the
skin. Albumen in the urine is common. Nervous symptoms, such as
convulsions, aphasia, delirium, and even catalepsy, have been
witnessed. In some cases there have been the symptoms of an irritant
poison--diarrhœa, vomiting, and pain in the bowels: in many cases
dilatation of the pupil has been observed.

[517] See “Death of Three Children by _S. nigrum_”; Hirtz., _Gaz. Med. de Strasbourg_, 1842; Maury, _Gaz. des Hôp._, 1864; J. B. Montane, _Chim. Med._, 1862; Magne, _Gaz. des Hôp._, 1869; Manners, _Edin. Med. Journ._, 1867. Cases of poisoning by bitter-sweet berries are recorded in _Lancet_, 1856; C. Bourdin, _Gaz des Hôpitaux_, 1864; Bourneville, the berries of _S. tuberosum_, _Brit. Med. Journ._, 1859.

Rabbits are killed by doses of ·1 grm. per kilo. The symptoms
commence in about ten minutes after the administration, and consist
of apathy and a low temperature; the breathing is much slowed.
Convulsions set in suddenly before death, and the pupils become
dilated. The _post-mortem_ appearances in animals are intense
redness and injection of the meninges of the cerebellum, of the
medulla oblongata, and the spinal cord. Dark red blood is found in
the heart, and the kidneys are hyperæmic. The intestinal mucous
membrane is normal.

§ 465. =Separation of Solanine from the Tissues of the
Body.=--Dragendorff has proved the possibility of separating
solanine from animal tissues by extracting it from a poisoned pig.
The best plan seems to be to extract with cold dilute sulphuric acid
water, which is then made alkaline by ammonia, and shaken up with
warm amyl alcohol. This readily dissolves any solanine. The peculiar
property possessed by the alkaloid of gelatinising, and the play of
colours with Fröhde’s reagent, may then be essayed on the solanine
thus separated.

5. CYTISINE.

§466. =The Cytisus Laburnum.=--The laburnum tree, _Cytisus laburnum_, so common in shrubberies, is intensely poisonous. The flowers, bark, wood, seeds, and the root have all caused serious symptoms. The active principle is an alkaloid, to which the name of Cytisine has been given. The best source is the seeds. The seeds are powdered and extracted with alcohol containing hydrochloric acid, the alcohol distilled off, the residue treated with water and filtered through a wet filter to remove any fatty oil, the filtrate treated with lead acetate; and, after separating the precipitated colouring matter, made alkaline with caustic potash, and shaken with amyl alcohol. The amyl alcohol is shaken with dilute hydrochloric acid, the solution evaporated, the crude crystals of hydrochloride thus obtained treated with alcohol to remove colouring matters, and recrystallised several times from water; it then forms well-developed, colourless, transparent prisms. From the hydrochloride the free base is readily obtained.

=Cytisine=, C₁₁H₁₄N₂O.--To cytisine used to be ascribed the formula C₂₀H₂₇N₃O, but a study of the salt and new determinations appear to prove that it is identical with ulexine.[518] Cytisine is in the form of white radiating crystals, consisting, when deposited from absolute alcohol, of anhydrous prisms, which melt at from 152° to 153°. Cytisine has a strong alkaline reaction; it is soluble in water, alcohol, and chloroform, less so in benzene and amyl alcohol, almost insoluble in cold light petroleum, and insoluble in pure ether. The specific rotatory power in solution is [α]_{D}17° = -119·57.

[518] A. W. Gerrard and W. H. Symons dispute this; they ascribe to ulexine the formula of C₁₁H₁₄N₂O, to cytisine C₂₀H₂₇N₃O. Ulexine is very hygroscopic, cannot be sublimed, even in a vacuum, without decomposition, and dissolves readily in chloroform; on the contrary, cytisine is not hygroscopic, sublimes completely, and is almost insoluble in chloroform, _Pharm. J._ (3), xx. 1017.

A. Partheil, _Ber._, xxiii. 3201-3203; _Arch. Pharm._, ccxxx. 448-498.

It is capable of sublimation in a current of hydrogen at 154·5°; the sublimate is in the form of very long needles and small leaflets; at higher temperatures it melts to a yellow oily fluid, again becoming crystalline on cooling. Cytisine is a strong base; it precipitates the earths and oxides of the heavy metals from solutions of the chlorides, and, even in the cold, expels ammonia from its combinations.

Cytisine forms numerous crystalline salts, among which may be mentioned two platinochlorides, C₁₁H₁₄N₂OH₂PtCl₆ + 2½H₂O and (C₁₁H₁₄N₂O)₂H₂PtCl₆, crystallising in golden yellow needles, which are tolerably soluble in water; and the aurochloride, C₁₁H₁₄N₂OHAuCl₄, crystallising in short, red-brown, hook-shaped needles; m.p. 212° to 213°, without evolution of gas.

§ 467. =Reactions of Cytisine.=--Concentrated sulphuric acid dissolves cytisine without colour; if to the solution is added a drop of nitric acid, it becomes orange-yellow, and on addition of a crystal of potassic bichromate, first yellow, then dirty brown, and lastly green. Concentrated nitric acid dissolves the base in the cold without colour, but, on warming, it becomes orange-yellow. Picric, tannic, and phosphomolybdic acids, potassic, mercuric, and potass. cadmium iodides, and iodine with potassic iodide, all give precipitates. Neither potassic bichromate nor mercuric chloride precipitates cytisine, even though the solution be concentrated. The best single test appears to be the reaction discovered by Magelhaes; this consists in adding thymol to a solution of cytisine in concentrated sulphuric acid, when a yellow colour, finally passing into an intense red, is produced.

§ 468. =Effects on Animals.=--W. Marmé found subcutaneous doses of from 30 to 40 mgrms. fatal to cats; death was from paralysis of the respiration, and could be avoided by artificial respiration. Cattle are sometimes accidentally poisoned by laburnum. An instance of this is recorded in the _Veterinarian_ (vol. lv. p. 92). In Lanark a storm had blown a large laburnum tree down to the ground; it fell into a field in which some young heifers were grazing, and they began to feed on the leaves and pods. Two or three died, and three more were ill for some time, but ultimately recovered.

The laburnum, however, does not always have this effect, for there is a case related in the _Gardeners’ Chronicle_, in which five cows browsed for some time on the branches and pods of an old laburnum tree that had been thrown aside. Rabbits and hares are said to feed eagerly, and without injury, on the pods and branches.

§ 469. =Effects on Man.=--The sweet taste of many portions of the laburnum tree, as well as its attractive appearance, has been the cause of many accidents. F. A. Falck has been able to collect from medical literature no less than 155 cases--120 of which were those of the accidental poisoning of children: only 4 (or 2·6 per cent.), however, died, so that the poison is not of a very deadly character.

One of the earliest recorded cases is by Christison.[519] A servant-girl of Inverness, in order to excite vomiting in her fellow-servant (the cook), boiled some laburnum bark in soup; very soon after partaking of this soup, the cook experienced violent vomiting, which lasted for thirty-six hours; she had intense pain in the stomach, much diarrhœa, and great muscular weakness; she appears to have suffered from gastro-intestinal catarrh for some time, but ultimately recovered.

[519] _Ed. Med. Journ._, 1843.

Vallance[520] has described the symptoms observed in the poisoning of fifty-eight boys, who ate the root of an old laburnum tree, being allured by its sweet taste. All were taken ill with similar symptoms, differing only in severity; two who had eaten half an ounce (nearly 8 grms.) suffered with especial severity. The symptoms were first vomiting, then narcosis, with convulsive movements of the legs and strange movements of the arms: the pupils were dilated. This dilatation of the pupil Sedgwick also saw in the poisoning of two children who ate the root. On the other hand, when the flower, seeds, or other portions of the laburnum have been eaten, the symptoms are mainly referable to the gastro-intestinal tract, consisting of acute pain in the stomach, vomiting, and diarrhœa. On these grounds it is therefore more than probable that there is another active principle in the root, differing from that which is in those portions of the tree exposed to the influence of sunlight.[521]

[520] _Brit. Med. Journ._, 1875.

[521] See also a case related by Dr. Popham, in which ten children ate laburnum seeds; the pupils were dilated. They all recovered. _B. and F. Med. Chir. Review_, Ap. 1863; also a case reported by H. Usher, _Med. Times and Gazette_, Sept. 15, 1862.

The _post-mortem_ appearances are, so far as known, in no way characteristic.

VII.--The Alkaloids of the Veratrums.

§ 470. The alkaloids of the veratrums have been investigated by Dr. Alder Wright, Dr. A. P. Luff, and several other chemists.[522]

[522] “The Alkaloids of the Veratrums,” by C. R. Alder Wright, D.Sc., and A. P. Luff, _Journ. Chem. Soc._, July 1879; “The Alkaloids of _Veratrum viride_,” by C. Alder Wright, D.Sc., _ib._, 1879.

The method which Wright and Luff adopted to extract and separate these alkaloids from the root of _V. album_ and _V. viride_, essentially consisted in exhausting with alcohol, to which a little tartaric acid has been added, filtering, distilling off the alcohol, dissolving the residue in water, alkalising with caustic soda, and shaking up with ether. The ethereal solution was next separated, and then washed with water containing tartaric acid, so as to obtain a solution of the bases as tartrates: in this way the same ether could be used over and over again. Ultimately a rough separation was made by means of the different solubilities in ether, pseudo-jervine being scarcely soluble in this medium, whilst jervine, veratralbine, veratrine, and cevadine are very soluble in it.

The yield of Wright and Luff’s alkaloids was as follows:--

TABLE SHOWING THE ALKALOIDS IN THE VERATRUMS.

+---------------+------------+---------------------+
| | V. album. | V. viride. |
| | Per Kilo. | Per Kilo. |
| +------------+---------------------+
|Jervine, | 1·3 grm. | ·2 grm. |
|Pseudo-jervine,| ·4 „ | ·15 „ |
|Rubi-jervine, | ·25 „ | ·02 „ |
|Veratralbine, | 2·2 „ | Traces. |
|Veratrine, | ·05 „ | Less than ·004 grm. |
|Cevadine, | Absent. | „ ·43 „ |
+---------------+------------+---------------------+

From whence it appears that _V. album_ has only a very small quantity of veratrine, that it is almost absent in _V. viride_; on the other hand, _V. viride_ contains a fair quantity of cevadine, an alkaloid absent in _V. album_.

Besides the six principles enumerated, G. Salzberger has recently separated two other crystalline substances, to which he has given the names of _protoveratrine_ and _protoveratridine_, and Pehkschen has also separated a ninth substance, to which he has given the name of _veratroidine_.

The formulæ of the nine bodies which have been separated from hellebore root are as follows:--

Melting-point.
1. Veratrine, C₃₇H₅₃NO₁₁, ...
2. Cevadine, C₃₂H₄₉NO₉, 205°-206°
3. Protoveratrine, C₃₂H₅₁NO₁₁, 245°-250°
4. Pseudo-jervine, { C₂₉H₄₃NO₇ (_Wright_), 299°-300°
{ C₂₉H₄₉NO₁₂ (_Pehkschen_), ...
5. Veratralbine, C₂₈H₄₃NO₅, ...
6. Protoveratridine, C₂₆H₄₅NO₈, 265°
7. Rubi-jervine, { C₂₆H₄₃NO₂ (_Wright_ and _Luff_), 236°
{ (_Salzberger_), 240°-245°
8. Jervine, C₂₆H₃₇NO₃2H₂O, 237°-239°
9. Veratroidine, C₃₂H₅₃NO₉, 149°

Three of these alkaloids possess powerful sternutatory properties, the least quantity applied to the nostrils exciting sneezing; the three are veratrine, cevadine, and protoveratrine.

Protoveratrine, C₃₂H₅₁NO₁₁, has been obtained by G. Salzberger[523] from powdered hellebore root, by the following process:--

[523] _Arch. Pharm._, ccxxviii. 462-483.

The powdered root is first freed from fatty and resinous matters by treatment with ether, and then the fat-free powder is exhausted with alcohol. The alcohol is evaporated off in a vacuum, the extract mixed with much acetic acid water, filtered from the insoluble residue, and treated with metaphosphoric acid; the voluminous precipitate contains much amorphous matter, with insoluble compounds of jervine and rubi-jervine. The precipitate is filtered off, and the filtrate treated with excess of ammonia and shaken up with ether. On separating the ether and distilling, protoveratrine crystallises out, and can be obtained pure by recrystallisation from strong alcohol.

Protoveratrine crystallises in four-sided plates, which melt with charring at 245° to 250°. The base is insoluble in water, benzene, and light petroleum; chloroform and boiling 96 per cent. alcohol dissolve it somewhat; cold ether scarcely touches it, boiling ether dissolves it a little.

Concentrated sulphuric acid dissolves the alkaloid slowly with the production of a greenish colour, which passes to cornflower blue, and, after some hours, becomes violet. Sulphuric acid and sugar gives a different colour to that produced by commercial veratrine. There is first a green colour which darkens into olive green, then becomes dirty green, and finally dark brown. When warmed with strong sulphuric, hydrochloric, or phosphoric acids, there is a strong odour of isobutyric acid developed. Dilute solutions of the salts are precipitated by ammonia, Nessler’s reagent, gold chloride, potassium mercury iodide, cadmium iodide, phosphotungstic acid, and picric acid; no precipitate is produced by tannin, platinum chloride, or mercuric chloride.

§ 471. =Veratrine= (C₃₇H₅₃NO₁₁) is a crystallisable alkaloid, which is a powerful irritant of the sensory nerves of the mucous membrane, and excites violent sneezing. Treated with concentrated sulphuric acid, it dissolves with a yellow colour, deepening into orange, then into blood-red, and finally passing into carmine-red. If the freshly-prepared sulphuric acid solution is now treated with bromine water, a beautiful purple colour is produced. Concentrated hydrochloric acid dissolves veratrine without the production of colour, but, with careful warming, it becomes beautifully red. This reaction is very delicate, occurring with ·17 mgrm. On saponification veratrine yields veratric acid.

Veratric acid is procatechu-dimethylether acid, and has the constitutional formula,

COOH
/
C₆H₃
\
(OCH₃)₂

Veratric acid forms colourless needles and four-sided prisms which have a marked acid reaction; it melts on heating to a colourless fluid, and sublimes without decomposition; it is easily soluble in hot alcohol, but insoluble in ether. If dissolved in nitric acid, water separates nitro-veratric acid, C₉H₉(NO₂)O₄ which crystallises out of alcohol in small yellow scales. Veratric acid unites with bases forming crystalline salts; the silver salt has the composition of C₉H₉AgO₄ = 37·37 per cent. silver, and may assist in identification. It is crystalline with a melting point of 205° to 206°.

=Cevadine=, C₃₂H₄₉NO₉ (Merck’s veratrine).--It has powerful sternutatory properties, and, under the influence of alcoholic potash, yields tiglic[524] acid and cevine, C₂₇H₄₃NO₈.

[524] Tiglic acid, C₅H₈O₂, is a volatile acid, m.p. 64°, boiling point, 198·5°; it forms a soluble barium salt, and an insoluble silver salt.

According to Ahrens, angelic acid is first formed, and then converted into tiglic acid. When the alkaloid is boiled with hydrochloric acid, tiglic acid is formed, and a ruby red mass. Nitric acid oxidises cevadine completely; with potassic permanganate it yields acetic and oxalic acids; with chromic acid it forms acetaldehyde and carbon dioxide.[525]

[525] _Ber._, xxiii. 2700-2707.

The Continental authorities always give to cevadine the name of veratrine. Cevadine forms a crystalline aurochloride, a crystalline mercurochloride, C₃₂H₄₉NO₉HHgCl₃, and a crystalline picrate, C₃₂H₄₉NO₉C₆H₃N₈O₇. The mercury salt crystallises in small silvery plates, and melts with decomposition at 172°. The picrate forms stable crystals blackening at 225°; both of the latter salts are but little soluble in water, but are soluble in alcohol. Cevadine also unites with bromine, forming a tetrabromide, an amorphous yellow powder insoluble in water, but readily soluble in alcohol, ether, and chloroform.

§ 472. =Jervine=, (C₂₆H₃₇NO₃2H₂O) (_Wright_ and _Luff_), C₁₄H₂₂NO₂ (_Pehkschen_),[526] crystallises in white needles, and, when anhydrous, melts at 237·7°. It is slightly lævorotatory. At 25° one part of the base dissolves in 1658 benzene, 268 ether, 60 chloroform, and 16·8 absolute alcohol. It is insoluble in light petroleum, and but slightly soluble in ethyl acetate, water, or carbon bisulphide. It forms a very insoluble sulphate, and a sparingly soluble nitrate and hydrochloride. Jervine gives, with sulphuric acid and sugar, a violet colour, passing to blue. Treated with strong sulphuric acid it dissolves to a yellow fluid, which becomes successively dark yellow, brownish yellow, and then greenish. The green shade is immediately developed by diluting with water. Jervine does not produce sneezing.

[526] _Jour. Pharm._ (5), xxii. 265-269.

§ 473. =Pseudo-jervine=, C₂₉H₄₃NO₇ (_Wright_), m.p. 299°; C₂₉H₄₉NO₁₂, m.p. 259° (_Pehkschen_), may be obtained in a crystalline state. One part is soluble in 10·9 parts of light petroleum, 372 parts of benzene, 1021 parts of ether, 4 of chloroform, and 185 of absolute alcohol. The pure base gives no colour with sulphuric, nitric, or hydrochloric acids. It does not produce sneezing.

§ 474. =Protoveratridine=, C₂₆H₄₅NO₈, is probably derived from protoveratrine. Salzberger[527] isolated it from powdered hellebore roots by treating the powder with barium hydroxide and water, and extracting with ether. The ether extract was separated and freed from ether in a current of hydrogen at a low temperature.

[527] _Arch. Pharm._, ccxxviii. 462-483.

From the dark green syrup obtained jervine crystallised out, and from the mother liquor ultimately protoveratridine was separated.